Single-cell transcriptome reveals the reprogramming of immune microenvironment during the transition from MASH to HCC

Metabolic dysfunction-associated steatohepatitis (MASH)-driven hepatocellular carcinoma (HCC) development is accompanied by the accumulation of immune cells within the hepatic microenvironment, yet its immunological networks remain obscure. Herein, we illustrate the profound reprogramming of the liver immune microenvironment during the transition from MASH to HCC by single-cell RNA sequencing (scRNA-seq). Overall design: A well-established MASH-driven HCC mouse model, STAM model, was first constructed. Thereafter, we applied single-cell RNA sequencing (scRNA-seq) analysis of CD45+ cells sorted from livers of mice with normal chow or at MASH stage, as well as paired paracancerous and cancer tissues from mice at HCC stage.

代谢功能障碍相关脂肪性肝炎（Metabolic dysfunction-associated steatohepatitis，MASH）驱动的肝细胞癌（hepatocellular carcinoma，HCC）发生过程中，肝脏微环境内会伴随免疫细胞的聚集，但其免疫网络仍尚不明确。本研究借助单细胞RNA测序（single-cell RNA sequencing，scRNA-seq），阐明了从MASH向HCC进展过程中肝脏免疫微环境的显著重编程。实验整体设计：首先构建了成熟的MASH驱动型肝细胞癌小鼠模型——STAM模型；随后对正常饮食小鼠、MASH阶段小鼠的肝脏分选得到的CD45阳性细胞，以及HCC阶段小鼠的配对癌旁组织与癌组织，开展了单细胞RNA测序（scRNA-seq）分析。